The treatment options for breast, ovarian, prostate and pancreatic cancer depend on several factors, including the stage, cancer subtype, and overall health. It is very important to know if you have a BRCA alteration as this will guide the treatment choices. These may include established chemotherapy drugs, targeted therapies such as PARP inhibitors, preventive surgery, or even entry into clinical trials.
Thanks to advances in scientific research, targeted therapies, such as PARP inhibitors, are now available for patients with breast, ovarian, pancreatic or prostate cancer linked to a mutation in the BRCA 1 and 2 genes. PARP is a protein (enzyme) found in our cells that helps damaged cells to repair themselves. As a cancer treatment, PARP inhibitors stop the PARP from doing its repair work in cancer cells and the cell dies. PARP inhibitors can only be considered after confirmation of the presence of BRCA 1/2 mutations. They are usually taken as tablets or capsules once or twice a day.
In the sections below we present only the main targeted therapies and specific treatment choices for breast, ovarian, prostate and pancreatic cancers linked to a mutation of the BRCA 1/2 genes.
Breast cancer
The prognosis and choice of treatment for breast cancer are mainly determined by the stage of the cancer, the degree of tumour differentiation and the receptor status. Oestrogen receptors (ET), progesterone receptors (PR), and the HER2 receptor are routinely tested. Other biomarkers may also influence the choice of therapy. In the case of ER negative (ER-), PR negative (PR-) and HER2 negative (HER2-) tumours, we speak of triple negative breast cancer (TNBC). Mutation analyses can be carried out to determine whether the cancer has a hereditary origin (BRCA or other mutation).
Carrying a mutation in the BRCA 1/2 genes has the following important consequences for today’s management of early breast cancer:
- Evaluate the addition of platinum-compounds
- Discuss neo- or adjuvant PARP inhibitors
- Consider mastectomy for affected breast and preventive contralateral mastectomy
- Discuss preventive salpingo-oophorectomy
- Adapt follow up.
- people with an inherited mutation in a different gene that repairs DNA damage (for example, PALB2, ATM or CHEK2).
- people who do not have an inherited gene mutation, but their tumour tested positive for an acquired mutation in a gene that repairs DNA damage.
Indications and admin info
As of July 1st 2023, the PARP inhibitor Olaparib is reimbursed for the adjuvant treatment of adult patients with high-risk HER2-negative early breast cancer and a germline BRCA1 or BRCA2 mutation. Olaparib is the first and only targeted treatment option that is approved for these patients. Patients are eligible after completion of treatment with an anthracycline and/or taxane in the (neo)-adjuvant setting. Reimbursement was granted based on the positive results of the OlympiA trial, in which adjuvant olaparib reduced the risk of invasive disease or death by 42% as compared to placebo.
Since July 1st, 2021, the PARP inhibitor Talazoparib is reimbursed as monotherapy for the treatment of adult patients with a germline BRCA1/2 mutation having locally advanced, unresectable, or metastatic triple negative (TNBC) or hormone-receptor positive/ HER2-negative breast cancer. Talazoparib is reimbursed in the first, second or later treatment line in the advanced breast cancer setting. In order to be eligible for reimbursement, the patient has to be previously treated with an anthracycline and/or a taxane in the (neo)adjuvant, locally advanced, or metastatic setting unless the patient is considered to be unsuitable for this treatment. In case of HR-positive breast cancer, the patient has to be pre-treated with hormone therapy, or should be unsuitable for this treatment modality. Importantly, the presence of a germline BRCA mutation needs to be confirmed by an accredited centre for medical genetics. The reimbursement of talazoparib in this setting is based on the results of the randomised, phase III EMBRACA trial.
Ovarian cancer
Ovarian cancer is a rare and aggressive cancer. In Belgium there are around 800 cases per year. While 85% of cases are sporadic, 10-15% are genetic and are linked to a BRCA 1 or 2 genetic mutation. Ovarian cancer treatment generally involves a combination of surgery and chemotherapy. Surgery for ovarian cancer has developed enormously and is currently considered the cornerstone of ovarian cancer treatment.
In addition to surgery and traditional chemotherapy, new targeted therapies have emerged in the treatment of ovarian cancer in recent years:
- Bevacizumab (Avastin®): this is an antibody directed against agents that stimulate the growth of blood vessels towards the tumour. It is administered as an infusion once every three weeks and is reimbursed in Belgium based on certain medical indications.
- Targeted therapies such as PARP inhibitors can also be administered. Oral PARP inhibitors for ovarian cancer treatment include Olaparib (Lynparza®). Other PARP inhibitors are under development.
Indications and admin info
Since 2015, the PARP inhibitor Olaparib has been reimbursed as maintenance treatment of platinum-sensitive relapsed high-grade ovarian cancer patients harbouring a BRCA1/2-mutation (germline and/or somatic). In 2020, this reimbursement was expanded to also include maintenance treatment of 1st line platinum-sensitive high-grade epithelial advanced ovarian cancer with a BRCA1/2-mutation (germline and/or somatic).
Prostate cancer
Nearly 10% of prostate cancer patients have BRCA2 gene alterations. BRCA1 or 2 alterations are especially common in men with metastatic hormone-resistant (or castration-resistant) prostate cancer. PARP inhibitors have shown clinical efficacy in patients with metastatic, hormone-resistant prostate cancer associated with alterations in genes encoding DNA damage response, with the greatest efficacy observed in those with BRCA alterations.
If a mutation in the BRCA1 or 2 genes is confirmed and other criteria are met (see yellow box below), targeted therapies such as PARP inhibitors can be administered. Oral PARP inhibitors for prostate cancer treatment currently include Olaparib (Lynparza®). Recently, an international study evaluated a new PARP enzyme inhibitor, Rucaparib, in patients with metastatic prostate cancer with BRCA2 gene alterations who have become resistant to hormone therapy. The results are promising.
Indications and admin info
From April 1st 2022 onwards, the PARP inhibitor Olaparib is reimbursed as monotherapy for the treatment of adult patients with metastatic castration-resistant prostate cancer and a BRCA1/2-mutation (germline and/or somatic) who have progressed following prior therapy with a new hormonal agent and are not eligible for a treatment with docetaxel (progression or intolerance or contra-indication) and cabazitaxel (contra-indication).
Pancreatic cancer
Pancreatic cancers associated with BRCA1/2 mutations have emerged as a distinct subgroup with sensitivity to other treatments and, in some cases, durable responses. Furthermore, beyond BRCA1/2 mutations, there is increasing recognition that other gene mutations may behave in a similar manner.
The body of evidence supporting the use of platinum-based therapy in patients carrying BRCA1/2 mutations is ever-growing. Also, in pancreatic ductal adenocarcinoma, the PARP inhibitor Olaparib has been approved as maintenance treatment in patients with germline BRCA mutations reaching disease control after a platinum-based first line chemotherapy (see yellow box below), proving significant benefit on progression free survival.
Indications and admin info
The PARP inhibitor Olaparib is also eligible for reimbursement as monotherapy for the maintenance treatment of adult patients with a germline BRCA1/2-mutations and a metastatic adenocarcinoma of the pancreas who did not progress after a minimum of 16 weeks of platinum within a first-line chemotherapy regimen. A confirmed or suspected deleterious germline mutation in the BRCA1/2 gene must be demonstrated by an approved centre for human genetics.
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Sources:
- Belgian Journal of Medical Oncology, VOLUME 15 | ISSUE 5 SEPTEMBER 2021
- Traitements systémiques du cancer du sein invasif : principes généraux pour les non-spécialistes du cancer
- NEW ONCOLOGY REIMBURSEMENT IN BELGIUM: OLAPARIB (LYNPARZA®)
- FORCE – Facing Our Risk of Cancer Empowered
- Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration
- Pancreatic Cancer: BRCA Targeted Therapy and Beyond
- CANCER DE L’OVAIRE (St Luc)
BRCA network asbl/vzw
